Antisense raf oligodeoxyribonucleotide is protected by liposomal encapsulation and inhibits Raf-1 protein expression in vitro and in vivo: implication for gene therapy of radioresistant cancer.
We have redesigned cationic liposomes by using a combination of dimethyldioctadecyl ammonium bromide, phosphatidylcholine and cholesterol to enhance the in vitro and in vivo effectiveness of antisense raf oligodeoxyribonucleotide (ODN). Circulating ODNs carried in vivo by liposomes were intact for at least 24 h, while free ODNs were undetectable after 5 min. Liposome-encapsulated antisense raf ODN (LE-ATG-AS) inhibited Raf-1 protein expression in vitro and in vivo. Furthermore, radioresistant tumor cells treated with LE-ATG-AS raf ODN were sensitized to ionizing radiation. These data provide new information for the delivery and potency of antisense ODN in vivo, and support the use of LE-ATG-AS raf ODN for gene therapy of radioresistant cancer.
Gokhale
P C
PC
Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC, USA.
Soldatenkov
V
V
Wang
F H
FH
Rahman
A
A
Dritschilo
A
A
Kasid
U
U
D000818:Animals; D002214:Capsules; D002412:Cations; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D015151:Immunoblotting; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D011836:Radiation Tolerance; D013873:Thionucleotides; D014407:Tumor Cells, Cultured
D002214:Capsules; D002412:Cations; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D019908:Proto-Oncogene Proteins c-raf